Summary: Decreased expression of fetal hemoglobin around the time of birth represents the defining mechanism in the clinical manifestation of sickle-cell and beta-thalassemia syndromes. Therefore, prevention or reversal of that process represents a major clinical goal for the treatment of those diseases. An ongoing interest of the laboratory involves the study of fetal hemoglobin expression and regulation as hematopoietic stem cells undergo differentiation to become erythroid progenitor and precursor cells. Several approaches are used to manipulate the expression of fetal hemoglobin including signal transduction, chemical induction, and genetic modulation of the fetal globin gene. A current focus arose from clinical transcriptome studies that identified the potential involvement of let-7 microRNA in the regulation of fetal hemoglobin. Studies are now underway to explore let-7 microRNA related biology with a goal of developing novel therapies for hemoglobin disorders.